The long range goal of this laboratory is to understand how the enzymic behaviors of arterial endothelial and smooth muscle cells act to maintain both arterial structural integrity and normal vascular tone. It has been suggested that repeated damage to the endothelial layer is a crucial step in the development of the atherosclerotic lesion, however, little is known about the mechanisms by which plasma components could cause such damage. The specific objective of the work proposed is to determine whether lysolecithin, occurring in elevated amounts in plasma during hyperlipemia, or in elevated local concentrations during lipolysis of chylomicrons or VLDL, may participate in damaging endothelial cells or altering their ability to carry out their regulatory functions. To explore this hypothesis, we plan to measure the capacity of cultured endothelial cells to cope with exogenous lysolecithin by degradation or reacylation; to determine the amount of cell-bound lysolecithin which is the threshold for lysis; and to determine the effects of sub-lytic amounts on crucial regulatory processes. The behavior of the endothelial cells will be compared to that of smooth muscle cultures from the same source, both to identify responses which are distinctive to either cell type, and to add to our knowledge of smooth muscle lipid metabolism.